Effects of High‐Fructose Consumption on Endothelial Progenitor Cell Function

Many studies have shown a causal relationship between high fructose diet and endothelial dysfunction. This dysfunction is likely a result of increased oxidative stress and subsequent decrease of nitric oxide (NO) bioavailability. We hypothesize that one of the factors contributing to endothelial dysfunction during fructose feeding (FF, isocaloric 60% fructose diet for 49 days) is impaired endothelial progenitor cell (EPC) proliferation, as EPC growth is known to be greatly affected by oxidative stress and NO imbalance. EPCs isolated from FF dogs (N=6) displayed impaired growth (32.8 ± 4.7 FF compared to 73.3 ± 4.1 control cells/mm2 after 2 weeks of culture). Proliferation of FF cells was partially rescued by treatment with AT1R blocker Losartan, suggesting the involvement of Angiotensin II. Scavenging of superoxide by Tiron also improved FF EPC growth, indicating oxidative stress as the cause of dysfunction. Finally, addition of Apocynin produced a similar rescue, indicating NADPH oxidase as the source of elevated oxidative stress. Increased oxidative stress in FF EPCs was confirmed by measurement of H2O2 level, revealing significantly higher concentration in FF cultures (40 ± 1 μM in control and 70 ± 4 μM in FF). H2O2 level was reduced to control with the addition of Losartan, Apocynin, OTC (a glutathione precursor), or the NO donor, SNAP. Supported by PO43023.